# Cohesin and chromosome translocation

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $36,561

## Abstract

This supplement is to support the training of Jeff Schoen, a Latino student from a disadvantaged
background, as he pursues a PhD in Cell Biology in the Rankin laboratory. The parent grant includes
studies of how the cohesin complex is regulated in response to cell cycle progression through modification
by the Esco acetyltransferase enzymes. The Rankin lab has had a long interest in cohesin regulation, in
particular in vertebrate-specific elaborations of cohesion control, and how cohesion is modified in
response to DNA damage.
The goal of this supplemental project is to determine how cohesin prevents translocation. Translocations
form when DNA double strand breaks are inappropriately repaired to unrelated DNA fragments, resulting
in gross genome rearrangement. Translocation is intrinsically mutagenic, and therefore correlated with
gene dysregulation and certain diseases such as cancer. We will define the underlying mechanisms with
the following specific experiments.
Aim 1. Determine how cohesin affects mobility of DNA double strand breaks. Model cell lines
have been developed in which sites adjacent to DNA double strand breaks can be monitored by live
and fixed cell microscopy. Using combination of inhibitors and RNAi we will exploit this system to
understand how and if cohesin impacts break mobility.
Aim 2. Measure the impact of cohesin and its regulators on translocation frequency. CRISPR-
Cas9 pairs will be used to induce double strand breaks on different chromosomes and translocation
frequency will be measured by quantitative PCR. We will use this system to understand which cohesin
regulators and chromatin environments affect translocation frequency.
Aim 3. Measure the impact of cohesin regulators on cohesin loading at DNA breaks.
Using inhibitors and depletions we will exploit a cell line with numerous inducible DNA double strand
breaks to identify critical upstream regulators of cohesin stabilization at DNA breaks.
The project described in this supplement proposal integrates well with that in the parent proposal. Here,
the student will undertake a study of how cohesin is regulated in response to DNA damage, focusing
particularly on the signaling and mechanisms upstream of cohesin itself.

## Key facts

- **NIH application ID:** 10315206
- **Project number:** 3R01GM101250-08S1
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Susannah Rankin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,561
- **Award type:** 3
- **Project period:** 2013-07-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315206

## Citation

> US National Institutes of Health, RePORTER application 10315206, Cohesin and chromosome translocation (3R01GM101250-08S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10315206. Licensed CC0.

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